The Leishmania donovani species complex is the causative agent of visceral leishmaniasis, which cause 20-40,000 fatalities a year. Here, we conduct a screen for balancing selection in this species complex. We used 384 publicly available L. donovani and L. infantum genomes, and sequence 93 isolates of L. infantum from Brazil to describe the global diversity of this species complex. We identify five genetically distinct populations that are sufficiently represented by genomic data to search for signatures of selection. We find that signals of balancing selection are generally not shared between populations, consistent with transient adaptive events, rather than long-term balancing selection. We then apply multiple diversity metrics to identify candidate genes with robust signatures of balancing selection, identifying a curated set of 24 genes with robust signatures. These include zeta toxin, nodulin-like, and flagellum attachment proteins. This study highlights the extent of genetic divergence between L. donovani complex parasites and provides genes for further study.
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http://dx.doi.org/10.1093/gbe/evab265 | DOI Listing |
Alzheimers Dement
December 2024
Department of Bioengineering, University of California, Los Angeles, CA, USA, Los Angeles, CA, USA.
Background: The initiation of amyloid plaque deposition signifies a crucial stage in Alzheimer's disease (AD) progression, which often coincides with the disruption of neural circuits and cognitive decline. While the role of excitatory-inhibitory balance is increasingly recognized in AD pathophysiology, targeted therapies to modulate this balance remain underexplored. This study investigates the effect of perampanel, a selective non-competitive AMPA receptor antagonist, in modulating neurophysiological changes in hAPP-J20 transgenic Alzheimer's mice.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The TaRget Enablement to Accelerate Therapy Development of Alzheimer's Disease (TREAT-AD) Centers are dedicated to identifying and validating targets from the NIH Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD). The centers develop Target Enabling Packages (TEPs) to explore new therapeutic target hypotheses, moving beyond the traditional focus on amyloid or tau pathologies. In accordance with open science principles, data, methods, and tools are freely shared with the research community via an open-access platform, the AD Knowledge Portal.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Rostock, Germany.
Background: Participatory research or patient and public involvement refer to the process of actively involving people with lived experience into the research process to improve its relevance, quality, and impact. In the PART project we aim to establish a sustainable structure to include underrepresented patient groups with neurodegenerative diseases into a patient advisory board for research. As one of our milestones, we conducted a systematic literature review with the aim of examining the impact of participatory research on people involved, such as those with cognitive impairment, caregivers, and researchers.
View Article and Find Full Text PDFNAR Genom Bioinform
March 2025
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Small proteins (≤100 amino acids) play important roles across all life forms, ranging from unicellular bacteria to higher organisms. In this study, we have developed SProtFP which is a machine learning-based method for functional annotation of prokaryotic small proteins into selected functional categories. SProtFP uses independent artificial neural networks (ANNs) trained using a combination of physicochemical descriptors for classifying small proteins into antitoxin type 2, bacteriocin, DNA-binding, metal-binding, ribosomal protein, RNA-binding, type 1 toxin and type 2 toxin proteins.
View Article and Find Full Text PDFCureus
December 2024
Neonatology Department, Daniel de Matos Maternity, Coimbra Local Health Unit, Coimbra, PRT.
Monochorionic twin pregnancies carry a risk of perinatal complications due to shared placental anastomoses, which can cause uneven blood distribution and lead to conditions like selective fetal growth restriction (sFGR). This case describes a monochorionic pregnancy complicated by preeclampsia and late-onset sFGR of twin B. Labor was prematurely induced and a 45% weight discordance between the twins was confirmed.
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